The role of type 2 herpes simplex virus (HSV-2) in human ocular infections was assessed. As an initial step, serotyping was carried out on all isolates from eye patients to determine the frequency with which HSV-2 could be isolated from human ocular infections. It is too early to draw a conclusion from the study at present. In normal rabbit eyes, systemic immunization with HSV provided complete protection against the production of primary uveitis by the intraocular injection of HSV; but in eyes that had had a bout of experimentally induced nonherpetic uveitis before the challenge, the same systemic immunization was not protective. In these eyes, an immune-mediated uveal inflammation developed. Nonherpetic uveitis had apparently "primed" the eyes of the HSV-immune rabbits for subsequent immune-mediated HSV uveitis. There was a cross-reaction between HSV-1 and HSV-2 in this phenomenon. Following the intravenous injection of 10 to the 5th power TCD50 of HSV-2, all of the young rabbits developed chorioretinitis and encephalitis. On the other hand, none of the adult rabbits developing these changes following the same procedure. The results strongly suggest that the age of the host exerts a strong influence on the induction of lesions in the eye and brain by HSV-2.